An important objective of the POl application is to define the contribution of altered sphingolipid metabolism in Acute Myeloid Leukemia (AML). Through the multiple Projects, the roles of specific sphingolipids and sphingolipid enzymes in AML and the efficacy of therapeutically targeting sphingolipid metabolism for AML will be defined. In order to achieve these objectives the Targeted Sphingomics Core will provide critical information to the Projects through two objectives; 1) The Core will quantify changes in the sphingolipidome (lipids and proteins), identifying new therapeutic targets for AML, and testing the efficacy of sphingolipid-based therapeutics and 2) the Core will provide standardized measurements of sphingolipids and their metabolizing enzymes for all four Projects. These objectives will create new hypotheses into the roles of sphingolipids in AML and serves to assist the Projects in testing their specific hypotheses. Taken together, this will lead to an understanding of the contributions of, and therapeutic efficacy of, targeting sphingolipid metabolism.